Our primary interest is in control mechanisms. We have been working in three major areas: 1) Control of the histidine operon. We have shown that histidyl-tRNA is an essential molecule in the control mechanism and we are studying the tRNA, synthetase, and other proteins in order to understand the mechanism of this control. We have developed a cell free system and have succeeded in making histidine biosynthetic enzymes in vitro, and in showing that this system is under control. We will now try to isolate the various components of this control. 2) We have found mutants that are lacking a pseudouridine in tRNA and that are derepressed for histidine biosynthesis, and leucine, isoleucine, and valine biosynthesis. We are purifying the enzyme involved in converting U to pseudoU and investigating the role of this conversion in control mechanisms for amino acid operons. 3) Super controls in the cell. We have been studying cyclicAMP, guanosine-tetra-phosphate, neuckotide and phosphate control in Salmonella. We are trying to generalize the ideas on super controls that have come out of the study of cyclicAMP. BIBLIOGRAPHIC REFERENCES: Ciesla, Z., Salvatore, F., Broach, J.R., Artz, S. W., and Ames, B.N. (1975) Histidine regulation in S. typhimurium XVI. A sensitive radiochemical assay for histidinol dehydrogenase. Anal. Biochem. 63, 44-55. Alper, M.D. and Ames, B.N. (1975) Cyclic AMP phosphodiesterase mutants of Salmonella typhimurium . J. Bacteriol. 122, 1081-1090.